Tumor suppressor p53 acts in many tumor types and induces
growth arrest or apoptosis depending on the physiological circumstances and cell type.
This protein is involved in the cell cycle regulation as a trans-activator. Abundance and
activity of the tumor suppressor p53 are regulated by many
different posttranslational modifications. Covalent modification with the small
ubiquitin- related protein (SUMO) is a one of these paths.

SUMO is a protein moiety that is ligated to lysine residues in a variety of target
proteins. The addition of SUMO can modulate the ability of proteins to interact with
their partners, alter their patterns of subcellular localization and control their
stability. Four different ubiquitous SUMO-related proteins have been identified in
mammalian cells [1]. It was shown that one of them, SUMO-1,
participates in p53 regulation [1].

In response to ionizing or UV-irradiation, cell cycle checkpoint kinase
2(Chk2) phosphorylates of
p53 on Ser-20 [2]. It stimulates, in turn,
SUMO-modification (sumoylation) of p53 [3].

SUMO-1 is activated by the specific activity of E1 ligase
(SAE1/2), which is a heterodimer comprising SUMO-1
activating enzyme subunits 1 and 2 (SAE1 and
Uba2). Subsequently, SUMO-1 is
transferred to E2-conjugating enzyme E2I [4].
Further, E2I transfers SUMO-1
tothe substrate p53. Data on
influence of sumoylation on activity p53 is contradictory.
According to some studies, that sumoylation activates p53[5], [6] according to others, the effect is inhibition [7] or
no effect [8].

It is shown that E3 ligases may participate in sumoylation. RING finger E3 ligases
PIAS are thought to facilitate direct transfer of
SUMO-1 from E2I to the
p53 [4]. It is shown that
PIAS proteins strongly repress the transcriptional activity
of p53 [7].

MDM2 is anubiquitin-protein
ligase E3. It ubiquitinates p53 and thus promotes
proteasomal degradation of p53 [9] and/or
blocks the interactions between p53 and
p53-activators(CREB-binding protein CBP
and E1A-binding protein p300) [10]. On the other hand, the mdm2 gene is a direct
target for binding and transcriptional activation by p53
[11]. When DNA in a cell is damaged by genotoxic stress,
p53 is phosphorylated at its amino terminus by kinases.
MDM2 cannot bind and ubiquitinylate phosphorylated
p53.

MDM2 is activated by sumoylation with participate
SAE1/2, E2I and some E3
ligases. E2I - MDM2 interaction
may be repressed by UV-irradiation [12]. Finally,
MDM2 is sumoylated during nuclear translocation by E3 ligase
- RanBP2 (nuclear pore protein) and then further sumoylated
once in the nucleus by other E3 ligases PIAS (nucleoplasmic
proteins) [13].

PML is a phosphoprotein that localizes to nuclear bodies
(NB) where it functions as a transcription factor and tumor suppressor.
PML sumolation led to recruitment
p53 and p53-activator CBP NB
[14]. CBP and co-activator
p300 in turn activates p53 by acetylation
[15], [16].

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